Immune Deficiency Syndromes in the Appalachia

Presented by: Demetrio R. Macariola, M.D. FAAP

THINK BEYOND THE BUGS

Disclosure Statement of Financial Interest

I, Demetrio R. Macariola , DO NOT have a financial

interest/arrangement or affiliation with one or more organizations that

could be perceived as a real or apparent conflict of interest in the

context of the subject of this presentation

Disclosure Statement of Unapproved/Investigative Use

I, Demetrio Macariola, DO/DO NOT anticipate discussing the

unapproved/investigative use of a commercial product/device during

this activity or presentation.

1. Describe the different immune deficiency syndromes in our community in outpatient

setting.2. Describe the pathogens associated with

each deficiency syndrome.

Learning Objectives

Immune Deficiency Syndromes in the Appalachia over 4 years

CVID: 20Agammaglobulinemia: 2Transient Hypogammaglobulinemia: 2Chronic Granulomatous Disease: 4Hyper IgE Syndrome: 2HIV: 1TOTAL: 35

“MY CHILD IS ALWAYS SICK”4 year old boy who developed pneumococcal pneumonia and bacteremia at 8 months later on developing E. coli UTI at 10 months and non typeable H. influenzae bacteremia at 2 years of age. Had been having recurrent pneumonia and sinusitis that mom thinks he cannot get over it.”. PE unremarkable.

LaboratoriesInitial immunoglobulin levels: IgM: low, IgG: normal, IgE: normal

After 2 weeks: immunoglobulin levels: IgM normal, IgG: low, IgE: normal

Diptheria and Tetanus titers: non protective

CD 19 lymphocyte count: normal

Differential Diagnosis?1. Common Variable Immunoglobulin Deficiency

2. Transient Hypogammaglobulinemia

3. Agammaglobulinemia

4. Hyper IgE Syndrome

Common Variable Immunoglobulin Deficiency

Infections usually occurs after 6 months

Can affect both genders

Non protective diphteria and tetanus titers

Treatment: Immunoglobulins

“Something not right is going on”2 month old boy previously healthy developed

right leg weakness after getting oral polio vaccine.

His dad is concern that “ something not right is going on”.

PE: right lower extremity weakness.

LaboratoriesInitial : IgM, IgG, IgA non detectable

Repeat: immunoglobulin levels non detectable

CD 19 lymphocyte count : zero

Differential Diagnosis

1. Agammaglobulinemia2. Transient hypogammaglobulinemia3. Hyper IgE syndrome4. Chronic granulomatous disease

Agammaglobulinemia

May be autosomal recessive or X-linkedAll immunoglobulins and CD 19

lymphocytes are non detectable.

“We belong to a family with immunoglobulin deficiencies”

9 month old girl who had 2 episodes of otitis media

within 3 months. No other infections. PE in

unremarkable. Two family members with CVID.

LaboratoriesIgA normal, low IgM IgG

Diphteria and tetanus titers: normal

CD 19 lymphocytes: normal

Differential Diagnosis1. Agammaglobulinemia

2. Transient hypogammaglobulinemia

3. Hyper IgE syndrome

4. Chronic granulomatous disease

Transient Hypogammaglobulinemia of Infancy (THI)

Low immunoglobulin levels that resolves between 2-3 years old.

Normal diphteria and tetanus titers

Normal CD 19 lymphocyte counts

“Rashes, asthma & infections not going away”

15-year-male presented with recurrent pneumonia and sinusitis.

Pneumatocele was observed in the chest Xray. Had several

episodes of sinusitis and pneumonia in the past. Had been

having moderate to severe asthma. PE findings pertinent for

eczema and crackles.

LaboratoriesIgG, IgM levels: normal

IgE level: 3000 mg/dl

Blood culture: S. aureus

Differential Diagnosis1. Agammaglobulinemia

2. Transient hypogammaglobulinemia

3. Hyper IgE syndrome

4. Chronic granulomatous disease

Hyper IgE SyndromeAlso known as Job syndrome

Eczema, asthma, recurrent sinusitis, lymphadenitis

Markedly elevated IgE level

Elevated eosinophils

“Unusual germ from a facial wound”3 year girl who developed cervical adenitis that did

not improved with amoxicillin-clavulanate. The cervical

adenitis recurred and was treated with trimethoprim-

sulfamethoxazole with improvement.

Laboratories:Wound culture: Burkholderia cepacia

Immunoglobulin levels: normal

Neutrophil oxidative burst test: positive

Differential Diagnosis1. Agammaglobulinemia

2. Transient hypogammaglobulinemia

3. Hyper IgE syndrome

4. Chronic granulomatous disease

Chronic Granulomatous DiseaseCan be autosomal recessive or x-linked

Rx: Trimethoprim-sulfamethoxazole, itraconazole

Gamma interferon

“My niece always have these skin bumps”

11 year old girl who lives with her aunt had been

having repeated skin infections for 2 years. Had

been on multiple antibiotics. Pertinent PE findings generalized

impetigo and oral thrush.

Laboratories:Immunoglobulin levels: Elevated IgM, IgE, IgA and

IgG

CD4 count: low

CBC: lymphopenia

Differential Diagnosis1. CVID

2. Hyper IgE syndrome

3. Hyper IgM syndrome

4. HIV

IMMUNOGLOBULIN DEFICIENCY SYNDROMES IN OUR AREA

1. Hypogammaglobulinemia- X-linked, autosomal recessive

2. Common Variable Immunoglobulin Deficiency

3. Transient Hypogammaglobulinemia of Infancy

4. Hyper IgE Syndrome/Job syndrome

Pathogens Commonly Affecting Patients with CVID and Agammaglobulinemia

1.Encapsulated bacteria: Pneumococcus, E.coli, H. influenzae, Salmonella, Mycoplasma

2. Viruses: enteroviruses, hepatitis C, CMV, VZV

3. Parasite: Giardia

Pathogens Commonly Affecting Patients with CGD

Bacteria: S. aureus, Serratia marcescens, B. cepacia, Nocardia.

Fungi: Aspergillus

Pathogens Commonly Affecting Patients with Hyper IgE

S. aureus

Chest xrayLobar Pneumonia Pneumatocele

Pathogens & Associated Conditions

E. coli sepsis: Galactosemia

Recurrent Neisseria infection: Terminal Complement Deficiency

Deep Candida Infection: Myeloperoxidase Deficiency

Disseminated Maycobacterial Infection: T lymphocyte Deficiency

P. jerovecii infection: T lymphocyte deficiency

Encapsulated bacterial infection: Splenic Dysfuntion

10 warning signs of Immune Deficiency Eight or more new ear infections within one year.

Two or more serious sinus infections within 1 year.

Two or more months on antibiotics with little effect.

Two or more pneumonias within 1 year.

Failure of an infant to gain weight or grow normally.

10 warning signs of Immune Deficiency Recurrent, deep skin or organ abscesses.

Persistent thrush in mouth or elsewhere on skin, after 1 year.

Need for intravenous antibiotics to clear infections.

Two or more deep-seated infections such as sepsis, meningitis or cellulitis.

A family history of primary immune deficiency.

Review QuestionA 4-year-old boy was diagnosed to have chronicgranulomatous disease which of the following may be used as prophylactic antibiotic treatment?A. ampicillinB. cephalexinC. trimethoprim-sulfamethoxazoleD. ceftriaxoneE. ertapenem

Review QuestionOn a 6-year-old boy with recurrent meningococcalinfection which of the following immune deficiency syndrome will you suspect?A. common variable immunoglobulin deficiencyB. complement deficiencyC. galactosemiaD. Job syndromeE. Bruton’s agammaglobulinemia

References:1. 2012 4th edition Principles and Practice of

Pediatric Infectious Diseases- Long, Pickering & Probe

2. 2012 edition AAP Red Book- Pickering

3. 2009 edition Principles and Practice of Infectious Diseases

4. Immune Deficiency Foundation Website- http://primaryimmune.org/

Special Thanks1. To Ms. Danielle Crumly- ID clinic nurse2. Colleagues3. Residents and medical students who had

rotated with pediatric ID.4. Nurses at Niswonger Children Hospital5. Nurses at ETSU Infusion Center